We are proposing that a transglutaminase-catalyzed cross-linking event, similar to the one occurring in Ca++-loaded human erythroctye and in cultured keratinocytes, occurs in cataract formation in lens. We shall explore molecular details of forming the gamma-glutamyl-epsilon-lysine cross-linked protein structures as well as regulatory aspects of activating or inhibiting the lens transglutaminase. The research will center on both senile and diabetic cataracts in man and in animal models.